HEMATOLOGY SYSTEM -

MEDICAL FACULTY UNHAS 2015

NUTRITIONAL ANEMIA

A. Yasmin Syauki
Nutritional Department
School of Medicine
Hasanuddin University
syaukiyasmin@gmail.com
 OBJECTIVE
To identify and manage iron deficiency
anemia
To identify and refer nutritional anemia of
megaloblastic
 OUTLINE
Preface
Iron deficiency anemia
Anemia megaloblastic :
Vitamin B12 deficiency
Folate deficiency
PREFACE
NUTRITIONAL ANEMIA

Anemia is :
not a disease
an expression of an underlying
disorder
the functional inability to supply
tissues with adequate oxygen,
usually due to decreased hemoglobin
level.
 HEMOGLOBIN, HEMATOCRIT/PCV
AND MCHC VALUE

Age of Group Hb Ht /PVC (%) MCHC

(g/dL)

Children 6 mos -6 11 33 34
yrs
Children 6 14 yrs 12 36 34

Adult male 13 39 34

Adult female 12 36 34

Pregnant woman 11 33 34
 CUT-OFF POINTS OF HEMOGLOBIN
CONCENTRATION OR HEMATOCRIT FOR THE
DIAGNOSIS OF ANAEMIA
Group Cut-off Hb for Cut-off Ht for
anaemia * anaemia **

Adult male < 130 g/L < 39%

Adult female < 120 g/L < 36%

Under-five children < 110 g/L < 33%

School children age < 12 years < 115 g/L < 34 %

School children age > 12 years < 120 g/L < 36 %

Pregnant women < 110 g/L < 33%

Lactating mothers < 120 g/L < 36%

*WHO, 2002
 METABOLIC CAUSES OF ANAEMIA

Microcytic anaemia Normocytic anaemia Macrocytic anaemia

(MCV < 75 fL) ( MCV 76-100 fL) (MCV > 100 fL)

Iron deficiency Haemolytic anaemia Folate/B12 deficiency

Lead poisoning Pernisious anaemia
Vitamin C deficiency
 Nutritional anemia arises :
Primary : Inadequate intake
Secondary :
Inadequate absorption (GI disease)
Inadequate utilization (cancer, infection)
Increase requirement (pregnancy, infancy,
childhood)
Increase excretion (liver disease)
IRON DEFICIENCY ANEMIA
(IDA)
 INTRODUCTION

Iron deficiency (ID) is one of the most frequent

nutrition deficiency all round the world.
Its prevalence is higher in children and
childbearing age women.
Iron deficiency anemia (IDA) mainly affects child
behavior and development, work performance
and immunity.
 ETIOLOGY

1. Increase requirement
infancy/childhood
pregnancy/lactation
preterm/SDF babies
2. Defective absorption
malabsorption
low levels of enhancers/increased levels of
inhibitors
achlorhydria/gastrectomy
 ETIOLOGY

3. Increase losses
occult bleeding/hookworm infestation
uterine causes
4. Diminished strores
preterm/SDF babies/ante partum hage
5. Decreased intake
poor diet
no breast feeding
babies in cows milk
anorexia of pregnancy
 SYMPTOMS AND SIGNS

Symptoms : pale, easily tired, lazy, sleep, fatigue,

weakness, anorexia, dysphagia, pica, chills.
Signs : pallor of conjuctiva and fore hands, angular
stomatitis, smooth tongue, glossitis,
koilonychia, low body temperature.
Functional indicator : decreased work capacity,
impairment in intelectual and behaviour
performance, more prone to infection, low birth
weight. Thermoregulation disturbances, prone to
lead poisoning
 DIAGNOSIS
Clinical and laboratory indices
Clinical features :
production of Hb : less oxygen reaches the
tissues especially the brain and heart muscle
causing pallor, tiredness, shortness of breath,
giddines, palpitations
Symptoms usually occur when Hb < 8 g/dl
- Epithelial abnormalities
angular stomatitis (cracked corners of mouth)
glossitis (sore tongue)
koilonychia (spoon-shaped nails)
 Fe Def Anemia

In severe cases may

have additional
physical exam
findings:
 DIAGNOSIS
Clinical and laboratory indices
Laboratory indices is the most common methods to assess
iron nutritional status
low hemoglobin
low hematocrit
low MCV, MCH, MCHC
normal or low reticulocyt count
serum iron 2.5 -10 umol/l
serum ferritin < 10 ng/ml
transferrin saturation <15%
TIBC > 350 ug/l
increased free erythrocyte protoporphyrin (100-600
ugm/l)
 Transferrin saturation (%) :

= serum iron (mol/L)/ TIBC (mol/L) x 100%

BLOOD SMEAR TEST
 Prelatent Latent IDA

Hemoglobin Normal Normal Decreased

MCV (80-100 fl) Normal Normal Decreased

MCHC (32-36%) Normal Normal Decreased or

normal
Iron absorption Increased Increased Increased
(10%)
% saturation Normal Decreased Decreased
(30-50) (<20)
Serum ferritin Decreased (<20) Decreased Decreased
(50-200 ug/l)
Iron stores Decreased Absent Absent
(1-3+) (0-1)
TIBC Increased Increased Increased (>400)
(300-360ug/dl) (>360) (>380)
 MANAGEMENT
The aim of treatment should be to
restore Hb levels and MCV to normal
Treatment of an underlying cause
should prevent further iron loss, but all
patients should have iron
supplementation both to correct
anaemia and replenish body stores.
 MANAGEMENT
ORAL
200 mg of iron daily before meal (e.g. 100 mg
twice daily).
How long?
14 days + (Hb required level Hb current level)
x4
half of the dose 3 months to restore iron reserve
Absorption
is enhanced: vitamin C, meat, orange juice,
fish
is inhibited: cereals, tea, milk
 MANAGEMENT
PARENTERAL IRON SUBSTITUTION
Bad oral iron tolerance (nausea, diarrhoea)
Negative oral iron absorption test
Necessity of quick management (CHD, CHF)
50 - 100 mg daily
I.v only in hospital (risk of anaphilactic shock)
I.m in outpatient department
iron to be injected (mg) = (15 - Hb/g%/) x body
weight (kg) x 3
 MANAGEMENT
Iron supplementation
Menstrual woman -> lost 30 mg -> need 1 mg Fe / day
Pregnant woman -> 900 mg for foetus, labour and
lactation-> need 2 mg Fe / day
Prevention :
1. Fe prophylaxis
2. Adequate intake of food sources of iron
3. Well planned family
4. Food fortification
5. Infestation eradication
IRON
 INTRODUCTION
Iron -> a metal, exist in several oxidation states
varying from Fe6+ to Fe2+, depending on its
chemichal environment.
The only states that are stable in the aqueos
environment of the body and in food are the ferric
(Fe3+) and the ferrous (Fe2+) forms.
Highly reactive element that can interact with
oxygen to form intermediates able to damage cell
membrane or degrade DNA.
Iron must be tightly bound to proteins to prevent
destructive effects.
 THE DISTRIBUTION AND FUNCTION
OF TOTAL BODY IRON
Site Function Amount of Percentage of
iron (mg) total body iron

Total body iron 3500 5000 100

Haemoglobin Oxygen transport 2500 60-70

Ferritin (2/3) and Iron storage: mainly liver , 1000 27

haemosiderin (1/2) spleen and bone marrow

Myoglobin Oxygen transporter in muscle 130 3.5

Uncharacterized iron- Storage 80 2.2

binding molecules

Cytochromes and Electron transport chain 8 0.2

other iron-containing cytochrome P450 (drug
enzymes metabolism),catalase
Transferrin Transport iron from intestines 3 0.08
to tissues
IRON METABOLISM
TRANSFER OF IRON TO THE CIRCULATION
AND TRANSPORT

Transferrin is the major protein responsible

for transporting Iron in the body.
Transferrin receptors, located on the
surface of nearly all cells in the body, can
bind two molecules of transferrin.
Transferrin saturation is important in
assessing ID.
TRANSFER OF IRON TO THE CIRCULATION
AND TRANSPORT

Tissues with higher requirements of Iron

(erythroid precursors, placenta and liver)
contain higher concentration of transferrin
receptors.
Once in tissues, Iron is stored as ferritin and
hemosiderin compounds, which are present
primarily in the liver, RE cells and bone marrow.
The amount of ferritin in storage compartment
depends on Iron status which ranges from
depleted to replete iron status
Ferritin concentration expresses Body Iron
Stores when assessing ID.
 DIETARY NEED
Only 10% of dietary iron is absorbed, therefore the
amount of digested daily is equal to the daily requirement
x 10.
The daily iron requirement

Group Requirement

Adult male 1.0 mg

Child 1.5 mg

Menstruating woman 2.0 mg

Pregnant woman 3,0 mg

AKG (2004) : 13- 26 mg
REGULATORY MECHANISMS OF IRON
ABSORPTION AND CELLULAR UPTAKE
Dietary Factors
Physico chemical form (ferrous form
better absorbed),
other dietary constituents (phosphates,
phytates, calcium, tannic acid, etc.),
Iron dose

Host-related conditions
 DIETARY FACTORS
Dietary sources of Iron can be classified as
food sources and fortified foods.
The amount of iron varies widely between
foods.
Iron exists in food under two forms,
Heme : in animal products (hemoglobin &
myoglobin), rapidly absorbed, about 10% of
iron consumed
non heme : mainly in plants, main source of
diet (90%), absorbed slowly, affected by
other factors
FORMS OF DIETARY
SOURCES OF IRON
 BIOAVAILABILITY
Heme iron, is readily absorbed.
Inorganic (non-heme) iron, is mostly in the oxidized
(Fe3+) state and must be reduced for absorption.
Factors affecting bioavailability :
Absorption is favoured in the ferrous as opposed to the
ferric form
Stomach hydrochloric acid and ascorbic acid both
favour absorption by reducing iron to the ferrous form
Increased erythropoetic activity (e.g due to bleeding)
increases absorption
Alcohol increases absorption
Phospates and phytates (from plants) form insoluble
complexes with iron and prevent absorption
 IRON ABSORPTION
Healthy Individuals: 5-10% absorbed
Iron deficiency : Up to 40% absorbed
Factors that affect absorption:
Enhancing factors /facilitators :
acid in the stomach
heme iron
high body demand
low body stores
meat protein factor
vitamin C
IRON ABSORPTION
Inhibiting factors/inhibitors :
low acidity in stomach
dietary fiber (phytate)
tannin in tea
oksalat
polifenol
calcium and phosphorus (food)
inadequate protein intake
 IRON ABSORPTION
Facilitators Inhibitors

Beef, lamb, pork, liver, +++ Wheat bran +++

chicken, fish
Tea +++
Orange, pear, apple,
pineapple juices +++/++ Nuts +++

Plum, banana, mango ++/+ Legumes +++

Carrot, potato, pumpkin, Leafy vegetables +++

broccoli, cauliflower, ++/+ Coffee +++/++
tomato
Maize +++/++
Salad (lettuce, tomato,
green pepper, cucumber) + Rice ++/+
Eggs +
Spinach +
 HOST RELATED FACTORS

The main factors regulating iron absorption :

Iron stores
The amount of iron to which intestinal cells
have been exposed
OTHER FACTORS INFLUENCING IRON
ABSORPTION

Rate of erythropoiesis
Physiological state
Gastric juice
VITAMIN C
 VITAMIN C
Powerful reducing agent :
Reduces dietary Fe 3+ to Fe 2+ in the
gut, allowing its absorption (therefore
deficiency can lead to anaemia)
 Source of Vitamin C

AKG : 75-90 mg/day (adult)

Sources
Citrus fruits
Tomatoes
Berries
Green vegetables
COPPER
 COPPER
Component of many enzymes

Oxidizing iron before it is transported (ceruloplasmin,

copper containing protein, required for normal
mobilization of iron from its storage site to the
plasma)

Plays role in mitochondrial energy production,

protection from oxidants, and synthesis pf melanine
and cathecolamine
 Source of Copper
Most diet provide 2mg/day
RDA 1.5 - 3mg/day
Food high in copper
Oysters, shellfish
Liver, Kidneys
Chocolate
Nuts
Dried legumes, Dried foods
Cereals
Poultry
ANEMIA MEGALOBLASTIC
 INTRODUCTION
Anemias characterized by distinctive
cytological and functional abnormalities in
peripheral blood film and bone marrow
cytology that is large cells of erythroid and
myeloid series due to impaired synthesis of
DNA
Etiological types :
vitamin B12 deficiency
folic acid deficiency
VITAMIN B12 DEFICIENCY
 ETIOLOGY
Reduced intake (e.g vegans because vitamin B12 only
found in animal derived foods)
Reduced absorption caused by :
A lack of intrinsic factor (e.g pernicious anaemia )
Diseases of the terminal ileum which is the site of
B12 absorption (e.g Chron disease or TB)
Bypass of the B12 absorption site (e.g fistulae or
surgical resection of gut)
Blind loop syndrome : parasites compete for B12
 DIAGNOSIS

Clinical and laboratory indices

Glossitis
Anorexia/diarrhea
Neurological involvement (peripheral
neurophaty and subacute combined
degeneration of spinal cord)
BLOOD SMEAR TEST
 DIAGNOSIS
Clinical and laboratory indices
Laboratory indices is the most common methods to
assess iron nutritional status
low hemoglobin
low RBC count
high MCV, MCH,
normal or low MCHC
high serum bilirubin
high serum iron
low serum vitamin B12
serum folate normal
Ig antibodies present (anemia pernicious)
high LDH
PERNICIOUS ANAEMIA
 ETIOLOGY
An autoimmune disorder where antibodies are made
to either :
Gastric parietal cells, causing atrophy or wasting
of the cells, thus preventing the production of
intrinsic factor and stomach acid
Intrinsic factor itself; antibodies bind to the intrinsic
factor, preventing it from either binding to vitamin
B12 (blocking antibodies) or binding to the
receptors in the terminal ileum (binding
antibodies). A lack of intrinsic factors lead to a
decreased uptake of vitamin B12.
CLINICAL SIGNS
Pernicious Anemia (PA)

Early graying of
hair
Blue eyes
Pernicious Anemia

Red beefy tongue

Pernicious Anemia

Vitiligo
PATHOLOGY ANATOMY
 PA

Normal Gastric atrophy

Atrophic Gastritis
DIAGNOSTIC
 SCHILLING TEST
Measures the absorption of vitamin B12
How to run :
Radioactive vitamin B12 given orally.
A 24 hr urine collection is performed to measure
the percentage of the dose of radioactive.
If the subject is vitamin B12 deficient, less than
10% will be excreted because vitamin B12 is being
used to replenish depleted stores.
If the result is abnormal, the test repeated with the
intrinsic factor.
If excretion is now normal, the diagnosis is
pernicious anaemia
 MANAGEMENT
Intramuscular injections of hydroxycobalamin
dor life.
Initially, these are more frequent to fill the
stores
VITAMIN B12
 FUNCTIONS
Vitamin B12 is a carrier of methyl groups.
It is coenzyme for two enzymes :
Methylmalonyl CoA mutase,
Homocysteine methyltransferase, as
methylcobalamin, to assist in the synthesis of
methionine.
 an intermediate of the citric
Important for DNA synthesis,
acid cycle, porphyrin synthesis
nervous tissue and fat metabolism
in the liver (Heme synthesis)
Absorption and
transport of vitamin
B12
Absorption and
transport of vitamin
B12
COBALT
 Cobalt
A component of vitamin B12 (cobalamin)
This vitamin is essential for maturation of red
blood cells and normal functioning of all cells
Requirement expressed in terms of Vit B12 : 1.4-
2 ug daily
Toxicity : intake of 10 to 20 ug/kg Body weight :
high intake cobalt in animal diet produce
polycytemia, bone marrow hyperplasia,
reticulocytosis, and increased blood volume
Deficiency: related to Vit B12 deficiency ---
macrocytic anemia
 Source of Cobalt

RDA 1.4 - 2.0 ug/day

Liver, kidney,
Oysters, clams
Poultry
Milk
FOLATE DEFICIENCY
 ETIOLOGY

1. Decreased intake
Decreased intake of raw/fresh vegetables by young
childre
Chronic alcoholics
2. Impaired absorption
Celiac disease
 ETIOLOGY
3. Increased demand
pregnancy
lactation
infancy
hemolysis
myeloproliferative disorders/malignancy
4. effect of drugs
folate antagonist (methotheraxate)
phenytoin/oral conceptive
 DIAGNOSIS

Clinical and laboratory indices

Glossitis
Anorexia/diarrhea
 DIAGNOSIS
Clinical and laboratory indices
Laboratory indices is the most common methods
to assess iron nutritional status
serum folate (<3 ng/ml)
RBC folate (<140 ng/ml)
rest all features similiar to vitamin B12
deficiency
FOLATE
 DIETARY FOLATE AND ITS
ABSORPTION
Degraded by prolonged boiling
Daily requirement roughly 100 mcg
Folate free diet causes deficiency in a few weeks
Absorption is largely through the jejenum
 COMPARISON OF VITAMIN B12 AND FOLATE
DEFICIENCY, MAIN DIFFERENCES

Characteristics Vitamin B12 Folate

Most common Pernicious dietary intake
cause anemia
Onset Slow, 20-30 years Develops over weeks
Neurological Frequent (+), Never
symptoms severe
Drug-related No : vitamin B12 Yes, anticonvulsants,
deficiency usually dihydrofolate reductase
causes inhibitors
secondary folate Folate deficiency occurs
deficiency frequently on its own
because intake or
demand
 MANAGEMENT
Vitamin B12 deficiency :
Intramuskular injections of hydroxycobalamin for
life
To fill the stores
Folate deficiency
Daily oral folate supplementation
Folic acid 5-10 mg/day
Cyanocobalamine 1000 ug 2 x
seminggu 250 ug/mgg-normal
Beware hypkalemia in severe cases
 MANAGEMENT
In pregnancy :
1. Folic acid 10 mg/day
2. severe anemia ---- transfusion
3. Fe tablet
Prevention in pregnant woman:
1. 300-500 ug folic acid with
2. 60 mg elemental Fe / day in last trimester
Reticc
ount
 REFERENCES
Sareen S. Grooper, et al. Advanced Nutrition and
Human Metabolism. Fifth Edition. 2009.
Lim Roach. Metabolism and Nutrition. Third
Edition. 2007
Umi Fahmida and Drupadi HS Dillon. Handbook
Nutritional Assessment. SEAMEO-TROPMED
RCCN. 2007